Atherosclerosis最新文献

{"title":"Effect of metabolic syndrome severity on cerebral haemodynamics and cognition in community-based cohort.","authors":"Mervin Tee, Mathijs B J Dijsselhof, Eddie Jun Yi Chong, Narayanaswamy Venketasubramanian, Christopher Chen, Jan Petr, Henk J M M Mutsaerts, Saima Hilal","doi":"10.1016/j.atherosclerosis.2025.120472","DOIUrl":"10.1016/j.atherosclerosis.2025.120472","url":null,"abstract":"<p><strong>Background and aims: </strong>Metabolic syndrome (METS) increases the risk of cognitive decline, but its impact on cerebral haemodynamics remains unclear. This study investigated relationships between continuous metabolic syndrome severity score (cMETS), cerebral haemodynamics, and cognition.</p><p><strong>Methods: </strong>In this cross-sectional study from the Epidemiology of Dementia in Singapore (EDIS) cohort, participants underwent neuropsychological assessments and arterial spin labelling MRI to evaluate cerebral haemodynamics, cognitive function, and composite metabolic syndrome severity (cMETS).</p><p><strong>Results: </strong>The study included 602 older adults (median age 69, IQR 64-74; 54 % female). Associations between cMETS and cerebral haemodynamics were observed (CBF: β = 0.40, p < 0.001; sCoV: β = -0.65, p < 0.001). Post-hoc analysis revealed a paradoxical relationship: in the lowest tertile, higher CBF was associated with higher cMETS (β = 0.80, p = 0.004), whereas in the highest tertile, lower CBF was associated with higher cMETS (β = -1.17, p = 0.015). Higher cMETS was associated with poorer global cognition (β = -0.15, p = 0.011), particularly in visuoconstruction and visuomotor speed. CBF was positively associated with global cognition (β = 0.01, p < 0.001) and mediated 43.5 % and 26.2 % of the cMETS-cognition relationship in the lowest and highest tertiles, respectively.</p><p><strong>Conclusion: </strong>These findings revealed associations of lower CBF specifically among individuals with higher cMETS. The observed mediation effect highlights the potential role of cerebral haemodynamics in the relationship between metabolic syndrome severity and cognitive performance. This demonstrates the complex interplay between metabolic factors and cerebral blood flow patterns in aging populations. Such nuanced associations warrant further investigation in longitudinal studies to better understand these relationships over time.</p>","PeriodicalId":8623,"journal":{"name":"Atherosclerosis","volume":"409 ","pages":"120472"},"PeriodicalIF":5.7,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144811664","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical impact of systemic inflammation across different high-sensitivity C-reactive protein cutoffs in patients undergoing percutaneous coronary intervention","authors":"Angelo Oliva ,&nbsp;Mark Shneyderman ,&nbsp;Mauro Gitto ,&nbsp;Samantha Sartori ,&nbsp;Birgit Vogel ,&nbsp;Benjamin Bay ,&nbsp;Kenneth Smith ,&nbsp;Pedro Moreno ,&nbsp;Joseph Sweeny ,&nbsp;Francesca Maria Di Muro ,&nbsp;Giulio Stefanini ,&nbsp;Annapoorna S. Kini ,&nbsp;George D. Dangas ,&nbsp;Samin K. Sharma ,&nbsp;Roxana Mehran","doi":"10.1016/j.atherosclerosis.2025.120523","DOIUrl":"10.1016/j.atherosclerosis.2025.120523","url":null,"abstract":"<div><h3>Background and aims</h3><div>Systemic inflammation enhances coronary atherosclerosis progression and is assessed by high-sensitivity C-reactive protein (hsCRP). However, heterogeneity exists in defining the optimal hsCRP threshold associated with increased cardiovascular risk. Here we evaluated the impact of inflammation in patients with CAD undergoing percutaneous coronary intervention (PCI) using different cutoffs of hsCRP elevation.</div></div><div><h3>Methods</h3><div>We conducted a retrospective analysis of patients undergoing PCI from 2012 to 2022 at Mount Sinai Hospital (NY, USA). Patients were stratified according to commonly used thresholds of baseline hsCRP. The primary endpoint was MACCE, defined as the composite of all-cause mortality, myocardial infarction, or stroke.</div></div><div><h3>Results</h3><div>Of 10,811 patients included, 6210 (57.4 %) had hsCRP &lt;2 mg/L, 1624 (15.0 %) between 2 and 3 mg/L, and 2977 (27.6 %) &gt; 3 mg/L. Increased rates of MACCE were observed in each group with elevated hsCRP using both the hsCRP = 3 mg/L (4.9 % vs. 2.6 %; <em>p</em> &lt; 0.001) and hsCRP = 2 mg/L thresholds (4.4 % vs. 2.4 %; <em>p</em> &lt; 0.001). The risk of MACCE was also higher in patients with hsCRP values between 2 and 3 mg/L (HR: 1.44, 95 % CI 1.03–2.00; <em>p</em> = 0.032). For both thresholds, the receiver operating characteristic (ROC) curve showed similar ability to predict MACCE.</div></div><div><h3>Conclusions</h3><div>In patients undergoing PCI, hsCRP values above both established thresholds of 2 and 3 mg/L predict an increased risk of 1-year MACCE, but neither threshold was superior in predicting cardiovascular risk. Patients with hsCRP between 2 and 3 mg/L have increased event rates compared to patients with hsCRP below 2 mg/L.</div></div>","PeriodicalId":8623,"journal":{"name":"Atherosclerosis","volume":"410 ","pages":"Article 120523"},"PeriodicalIF":5.7,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145263282","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Selective removal of 7-ketocholesterol by a novel atherosclerosis therapeutic candidate reverts foam cells to a macrophage-like phenotype.","authors":"Prerna Bhargava, Darren Dinh, Fadzai Teramayi, Ana Silberg, Noa Petler, Amelia M Anderson, Keivan Sadrerafi, Daniel M Clemens, Matthew S O'Connor","doi":"10.1016/j.atherosclerosis.2025.119217","DOIUrl":"10.1016/j.atherosclerosis.2025.119217","url":null,"abstract":"<p><strong>Background and aims: </strong>The removal of the toxic oxidized cholesterol, 7-ketocholesterol (7KC), from cells through the administration of therapeutics has the potential to treat atherosclerosis and various other pathologies. While cholesterol is a necessary building block for homeostasis, oxidation of cholesterol can lead to the formation of toxic oxysterols with 7KC being the most prominent. 7KC is primarily formed through the non-enzymatic oxidation of cholesterol and is found in high levels in oxidized LDL (oxLDL) particles, which are highly implicated in heart disease. 7KC is implicated in the pathogenesis of numerous diseases, including multiple sclerosis, hypercholesterolemia, sickle cell anemia, and multiple age-related diseases. Of particular interest is the role of 7KC in the progression of atherosclerosis, with several studies associating elevated 7KC levels with the etiology and severity of the disease and in the underlying transition of macrophages to foam cells.</p><p><strong>Methods: </strong>This research aims to elucidate the molecular mechanisms of UDP-003, a novel therapeutic compound, in mitigating the harmful effects of 7KC in mouse and human monocyte and macrophage cell lines.</p><p><strong>Results: </strong>Experimental evidence demonstrates that administration of UDP-003 can reverse the foam cell phenotype, rejuvenating these cells by returning phagocytic function, preventing loss in efferocytosis ability, and decreasing both reactive oxygen species (ROS) and intracellular lipid droplet accumulation. We further demonstrate that UDP-003 drives urinary excretion of 7KC in vivo and has a safety/toxicity profile compatible with initiation of human clinical trials.</p><p><strong>Conclusions: </strong>Our data suggest that the targeted removal of 7KC from foam cells with UDP-003 can potentially prevent and reverse atherosclerotic plaque formation. UDP-003 has the potential to be the first disease-modifying therapeutic approach to treating atherosclerotic disease.</p>","PeriodicalId":8623,"journal":{"name":"Atherosclerosis","volume":" ","pages":"119217"},"PeriodicalIF":5.7,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144109490","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ethnic differences in coronary plaque burden and characteristics: A matched CCTA cohort study of South Asians and non-Hispanic Whites.","authors":"Venkat Sanjay Manubolu, April Kinninger, Suvasini Lakshmanan, Suraj Dahal, Keishi Ichikawa, Dhiran Verghese, Luay Alalawi, Jairo Aldana, Shriraj Susarla, Hoon J Seok, Chris Dailing, Sion K Roy, Anand Rohatgi, James P Earls, Matthew J Budoff","doi":"10.1016/j.atherosclerosis.2025.120455","DOIUrl":"10.1016/j.atherosclerosis.2025.120455","url":null,"abstract":"<p><strong>Background/aims: </strong>South Asians (SA) experience a significantly higher incidence of atherosclerotic cardiovascular disease (CVD) events compared to non-Hispanic whites (NHW). However, detailed plaque characteristics in SA, particularly assessed through quantitative coronary plaque analysis using coronary computed tomography angiography (CCTA), remain under-investigated. This study aimed to compare the characteristics of coronary plaque burden between SA and NHW using CCTA.</p><p><strong>Methods: </strong>In this cross-sectional study, we identified 165 SA subjects at our institution who underwent CCTA and matched them 1:1 for age, sex, BMI and diabetes mellitus with NHW. Quantitative coronary plaque analysis was reported by plaque subtypes in percent atheroma volume (PAV) and absolute plaque volumes. Kruskall-Wallis test was used to analyze the plaque volumes and PAV between the matched cohorts.</p><p><strong>Results: </strong>A total of 330 subjects (mean age: 65 ± 9.9 years; 74 % male; 32 % with diabetes) formed the study population. SA had higher total plaque PAV (median [IQR]: 11.9 [4.4, 22.0] vs. 6.2 [2.4, 14.2]), NCP PAV (5.1 [3.2, 8.1] vs. 3.8 [1.8, 6.5]), and calcified plaque PAV (4.9 [1.4, 12.7] vs. 2.4 [0.3, 7.5]) than NHW (p < 0.0001). Differences were significant for those under 55 and 65 years but not in those ≥65, except for calcified plaque PAV when stratified by age.</p><p><strong>Conclusion: </strong>Younger SA (<55 years) exhibited higher total, non-calcified, and calcified plaque burden compared to NHW, suggesting earlier CAD risk. CCTA may aid early detection and support aggressive prevention strategies in this high-risk population.</p>","PeriodicalId":8623,"journal":{"name":"Atherosclerosis","volume":" ","pages":"120455"},"PeriodicalIF":5.7,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144717283","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Repeated measurement of lipoprotein(a): technical versus biological variability.","authors":"Adriana Koller, Cathrin Pfurtscheller, Azin Kheirkhah, Klaus J Stark, Martina E Zimmermann, Iris M Heid, Florian Kronenberg","doi":"10.1016/j.atherosclerosis.2025.120456","DOIUrl":"10.1016/j.atherosclerosis.2025.120456","url":null,"abstract":"<p><strong>Background and aims: </strong>Repeated measurements of Lp(a) concentrations are not considered relevant since Lp(a) is expected to remain relatively stable during life through the strong genetic determination. This has recently been questioned by reports showing major fluctuations of Lp(a) over time. However, these studies have not distinguished between biological or technically caused variability. Therefore, this study aimed to assess the biological variability of Lp(a) concentrations over time while minimizing technical variability to evaluate the clinical relevance of repeated Lp(a) measurements.</p><p><strong>Methods: </strong>Lp(a) concentrations were measured in duplicates in 715 elderly people with two blood collections 3.2 years apart and having the sample pairs (baseline and follow-up) on the same assay plate.</p><p><strong>Results: </strong>The Lp(a) concentrations of sample pairs were strongly correlated (r = 0.98). We grouped individuals according to risk categories from the baseline Lp(a) measurement of <30, 30 to <50, 50 to <70 and ≥ 70 mg/dL and observed that between baseline and follow-up 655 of the 715 individuals (91.6 %) remained in their risk category, while 33 (4.6 %) moved to a higher and 27 (3.8 %) to a lower category. We calculated that each 5 mg/dL incorrectly measured Lp(a) concentration results in a 1 % miscalculation of the lifetime cardiovascular risk. This is relatively small considering that roughly a third of the population is dying from cardiovascular disease.</p><p><strong>Conclusions: </strong>Clinically relevant changes of Lp(a) concentrations by biological variability do not occur frequently in an elderly population. Major changes of Lp(a) as reported in the literature might be caused by technical rather than biological fluctuations and argues for repeated Lp(a) measurements in specific cases and an improvement of the quality control measures in laboratory practice.</p>","PeriodicalId":8623,"journal":{"name":"Atherosclerosis","volume":" ","pages":"120456"},"PeriodicalIF":5.7,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144759026","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"2025 focused update of the 2019 ESC/EAS guidelines for the management of dyslipidemias - Advancing evidence-based care through innovation.","authors":"Florian Kronenberg, Jan Borén, Kausik K Ray","doi":"10.1016/j.atherosclerosis.2025.120487","DOIUrl":"10.1016/j.atherosclerosis.2025.120487","url":null,"abstract":"","PeriodicalId":8623,"journal":{"name":"Atherosclerosis","volume":" ","pages":"120487"},"PeriodicalIF":5.7,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144940504","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Influence of a mitochondria-associated membranes (MAMs) linker protein on coronary calcification: Commentary on \"GRP75 inhibition attenuates arterial calcification\" by Heyn J et al. Atherosclerosis 2025.","authors":"Florence Gizard, Nassim Mohamedi","doi":"10.1016/j.atherosclerosis.2025.120497","DOIUrl":"https://doi.org/10.1016/j.atherosclerosis.2025.120497","url":null,"abstract":"<p><p>Heyn et al. provided the first evidence of a key role for a MAM component, the Glucose-regulated protein 75 (GRP75), in coronary calcification. The underlying mechanisms involve the GRP75 effect on MAM integrity and matrix mineralization in calcifying vascular smooth muscle cells (SMCs). These innovative data open up new avenues for biomedical research on atherosclerosis, and possibly other chronic and/or rare diseases.</p>","PeriodicalId":8623,"journal":{"name":"Atherosclerosis","volume":"409 ","pages":"120497"},"PeriodicalIF":5.7,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145306781","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Response Letter.","authors":"Ole Fröbert, Ida B Pedersen, Astrid J Hjelholt, Christian Erikstrup, Sara Cajander","doi":"10.1016/j.atherosclerosis.2025.120499","DOIUrl":"https://doi.org/10.1016/j.atherosclerosis.2025.120499","url":null,"abstract":"","PeriodicalId":8623,"journal":{"name":"Atherosclerosis","volume":"409 ","pages":"120499"},"PeriodicalIF":5.7,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145306813","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"GRP75 inhibition attenuates arterial calcification.","authors":"Jonas Heyn, Andrea Gorgels, Nicolas Hense, Alexander Gombert, Eva Miriam Buhl, Lisa Stark, Sonja Vondenhoff, Joel Simon, Heidi Noels, Nikolaus Marx, Claudia Goettsch","doi":"10.1016/j.atherosclerosis.2025.119243","DOIUrl":"10.1016/j.atherosclerosis.2025.119243","url":null,"abstract":"<p><strong>Background and aims: </strong>Arterial calcification is a risk factor for cardiovascular mortality. The calcification process is driven by the osteogenic transition of vascular smooth muscle cells (SMCs), which release extracellular vesicles (EVs) that act as mineralization nucleation sites. While mitochondrial dysfunction and endoplasmic reticulum (ER) stress have been implicated in arterial calcification, the role of their contact sites remains unknown. Mitochondria-associated membranes (MAMs) are inter-organelle contacts connecting the outer mitochondrial membrane to the ER membrane through protein-protein interactions. This study investigated the role of Glucose-regulated protein 75 (GRP75), a MAM linker protein, in SMC calcification and EV cargo.</p><p><strong>Methods: </strong>Human coronary artery SMCs were cultured in osteogenic medium to induce calcification. MAMs were isolated from SMCs and human carotid artery by subcellular fractionation and visualized using transmission electron microscopy. SMC-derived EVs were isolated from the conditioned culture medium by ultracentrifugation. GRP75 inhibition was achieved using silencing RNA or the inhibitor MKT-077. Mitochondrial respiration and ER stress were analyzed using Seahorse analysis and Western blotting.</p><p><strong>Results: </strong>Calcifying SMCs expressed higher GRP75 mRNA (2.2-fold ± 0.7, p = 0.043) and protein (1.3-fold ± 0.2, p = 0.008) levels compared to control SMCs. GRP75 was enriched at MAMs, and electron microscopy imaging demonstrated closer mitochondria-ER contacts in both calcifying SMCs in vitro and human calcified carotid artery specimens. GRP75 inhibition by silencing RNA (-35 % ± 13 %, p < 0.001) or MKT-077 (-57 % ± 3 %, p < 0.001) attenuated matrix mineralization and reduced close mitochondria-ER contacts along with attenuating mitochondrial respiration capacity. Additionally, GRP75 was enriched in EVs released by calcifying SMCs (1.3-fold ± 0.1, p = 0.040).</p><p><strong>Conclusions: </strong>Our findings demonstrate that MAMs are altered in calcifying SMCs. GRP75 inhibition disrupted close mitochondria-ER contact formation, decreased mitochondrial respiration, modulated the osteogenic transition of SMCs, and reduced vascular calcification. Therefore, GRP75 could serve as a potential target for preventing arterial calcification.</p>","PeriodicalId":8623,"journal":{"name":"Atherosclerosis","volume":" ","pages":"119243"},"PeriodicalIF":5.7,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144131848","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"2025 Focused Update of the 2019 ESC/EAS Guidelines for the management of dyslipidaemias.","authors":"François Mach, Konstantinos C Koskinas, Jeanine E Roeters van Lennep, Lale Tokgözoğlu, Lina Badimon, Colin Baigent, Marianne Benn, Christoph J Binder, Alberico L Catapano, Guy G De Backer, Victoria Delgado, Natalia Fabin, Brian A Ference, Ian M Graham, Ulf Landmesser, Ulrich Laufs, Borislava Mihaylova, Børge Grønne Nordestgaard, Dimitrios J Richter, Marc S Sabatine","doi":"10.1016/j.atherosclerosis.2025.120479","DOIUrl":"10.1016/j.atherosclerosis.2025.120479","url":null,"abstract":"","PeriodicalId":8623,"journal":{"name":"Atherosclerosis","volume":" ","pages":"120479"},"PeriodicalIF":5.7,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144940388","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}